Multiple myeloma clinical trials exclude patients with the highest-risk disease: a systematic review of trial exclusion criteria.

Patients with certain subsets of multiple myeloma continue to have poor outcomes and are in need of novel treatment approaches. Strict eligibility criteria for randomized controlled trials (RCTs) limit access to clinical trials and limit the external validity of trial results for these patients. We systematically reviewed RCTs in newly diagnosed myeloma from 2006 to 2023 to ascertain the prevalence of 12 key exclusion criteria and trends over time. 80 RCTs were included. Exclusion criteria included: age in 43 (51%) trials; projected life expectancy in 20 (24%); performance status in 74 (87%); non-secretory and/or oligosecretory disease in 47 (55%), hepatic function in 64 (79%), renal function in 63 (74%), hematological thresholds in 50 (59%), prior malignancy in 68 (80%), and neuropathy in 50 (59%). For 53 trials which had detailed exclusion criteria available, plasma cell leukemia was excluded in 21 (40%), extramedullary disease in 5 (9%) and CNS disease in 13 (25%). The percentage of studies invoking each of these exclusion criteria did not significantly improve over time on univariate regression analysis, and exclusion criteria relating to neuropathy have worsened. The restrictive eligibility criteria of most myeloma RCTs perpetuate a cycle where limited data exists to treat challenging myeloma subtypes.

Patients with atrial fibrillation and common exclusion criteria from clinical trials are at high risk of clinical events: the Murcia AF Project II (MAFP-II) cohort study.

BACKGROUND: Some clinical characteristics and comorbidities in atrial fibrillation (AF) patients are exclusion criteria in randomized clinical trials (RCTs) investigating oral anticoagulants (OAC). However, these conditions are present also in everyday clinical practice patients. We compared the risk of adverse clinical outcomes between patients with and without RCT exclusion criteria. METHODS: The Murcia AF Project II was an observational cohort study including AF outpatients starting vitamin K antagonists (VKAs) from July 2016 to June 2018. For the selection of the exclusion criteria, the four pivotal RCTs of direct-acting OAC (DOACs) were used as reference. During 2 years, all ischemic strokes/transient ischemic attacks, major adverse cardiovascular events (MACEs), major bleeds, and all-cause deaths were recorded. RESULTS: 1050 patients (51.5% female, median age 77 years) were included, of whom 368 (35%) met at least one exclusion criterion for RCTs. During follow-up, the incidence rate ratios for major bleeding, MACE and all-cause mortality were higher among patients with exclusion criteria (all p < 0.001). Patients fulfilling at least one exclusion criterion had increased risks of major bleeding (aHR 1.48; 95% CI 1.22-1.81; p < 0.001), MACE (aHR 1.51, 95% CI 1.10-2.09, p = 0.012), and mortality (aHR 3.22, 95% CI 2.32-4.48, p < 0.001), as well as a lower event-free survival (all log-rank p < 0.001). CONCLUSIONS: In this AF cohort taking VKAs, more than one-third had at least one RCT exclusion criteria, which translates into higher risk of major bleeding, MACE, and death. These observations should be considered when translating RCTs results to AF patients for a proper and a more patient-centered management.

Eligibility for Substance Use Clinical Trials Among Emergency Psychiatry Patients: The Impact of Exclusion Criteria.

Objective: The first objective was to identify common exclusion criteria used in clinical trials. The second objective was to quantify the degree to which these criteria exclude emergency psychiatry patients. Methods: Qualitative Content Analysis was used for the first objective, identifying common exclusion criteria used in recent high-impact substance use clinical trials. A retrospective record review was used for the second objective, which examined the frequency of these exclusion criteria in a 1-month sample of adults receiving psychiatric evaluation in an emergency department. Results: Most trials had exclusions for co-occurring psychiatric problems (76.6%), medical problems (74.0%), prior or current treatment (72.7%), motivation for change (61.1%), pregnancy or lactation (57.1%), or using other specified substances of abuse (54.6%). In the clinical sample, exclusions for co-occurring psychiatric problems would make 94.7% of patients ineligible. Other exclusions had a combined effect of making 76% of patients ineligible. Conclusions: Clinical trials using typical exclusion criteria exclude nearly all emergency psychiatry patients with substance use problems.

The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis-Recommended criteria and literature review.

After two multistate outbreaks of allograft tissue-transmitted tuberculosis (TB) due to viable bone, evidence-based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.

Which patients should be considered for gene therapy.

Gene therapy for haemophilia, utilizing adeno-associated viral vectors (AAVs) and coagulation factor genes, have demonstrated promising results, leading to recent approvals and introduction of the first gene therapy products into clinical practice. For successful and safe use, there are predefined inclusion and exclusion criteria, and the treatment process and associated risks should be thoroughly understood and long-term safety and efficacy carefully evaluated during follow up. As gene therapy becomes more accessible outside of clinical study centers, continuous evaluation of patient eligibility for subsequent AAV-based treatments becomes essential. Thorough evaluation of factors such as liver condition, anti-AAV status, and medical history ensures that gene therapy maximizing benefits while minimizing risks. Apart from fulfilling the established inclusion and exclusion criteria, the success of gene therapy is greatly influenced by the motivation and willingness of patients to accept temporary constraints, such as regular laboratory monitoring, potential use of immunosuppressants, and thorough documentation. Furthermore, various patient-related factors play a significant role in the management and outcomes of gene therapy, making a comprehensive evaluation essential. With the accumulation of more data, there is potential for the expansion of certain inclusion criteria, which may allow for a larger number of eligible patients to benefit from gene therapy. Empowering patients through shared decision-making enables them to thoroughly consider the therapy's potential benefits and risks.

Clinical Trials Studying Suicide Risk Reduction: Who is Excluded From Participation.

OBJECTIVE: The use of exclusion criteria in clinical trials can cause research participants to differ markedly from clinical populations, which negatively impacts generalizability of results. This study identifies and quantifies common and recurring exclusion criteria in clinical trials studying suicide risk reduction, and estimates their impact on eligibility among a clinical sample of adults in an emergency department with high suicide risk. METHOD: Recent trials were identified by searching PubMed (terms suicide, efficacy, effectiveness, limited to clinical trials in prior 5 years). Common exclusion criteria were identified using Qualitative Content Analysis. A retrospective chart review examined a one-month sample of all adults receiving psychiatric evaluation in a large urban academic emergency department. RESULTS: The search yielded 27 unique clinical trials studying suicide risk reduction as a primary or secondary outcome. After research fundamentals (e.g. informed consent, language fluency), the most common exclusion criteria involved psychosis (77.8%), cognitive problems (66.7%), and substance use (63.0%). In the clinical sample of adults with high suicide risk (N = 232), psychosis exclusions would exclude 53.0% of patients and substance use exclusions would exclude 67.2% of patients. Overall, 5.6% of emergency psychiatry patients would be eligible for clinical trials that use common exclusion criteria. CONCLUSIONS: Recent clinical trials studying suicide risk reduction have low generalizability to emergency psychiatry patients with high suicide risk. Trials enrolling persons with psychosis and substance use in particular are needed to improve generalizability to this clinical population.

Exclusion criteria limit who can enroll in trials studying suicide risk reduction.Trials most frequently exclude psychosis, cognitive problems, and substance use.Trials have poor generalizability to emergency psychiatry patients.

Enhanced SpO2 estimation using explainable machine learning and neck photoplethysmography.

Reflectance-based photoplethysmogram (PPG) sensors provide flexible options of measuring sites for blood oxygen saturation (SpO2) measurement. But they are mostly limited by accuracy, especially when applied to different subjects, due to the diverse human characteristics (skin colors, hair density, etc.) and usage conditions of different sensor settings. This study addresses the estimation of SpO2 at non-standard measuring sites employing reflectance-based sensors. It proposes an automated construction of subject inclusion-exclusion criteria for SpO2 measuring devices, using a combination of unsupervised clustering, supervised regression, and model explanations. This is perhaps among the first adaptation of SHAP to explain the clusters gleaned from unsupervised learning methods. As a wellness application case study, we developed a pillow-based wearable device to collect reflectance PPGs from both the brachiocephalic and carotid arteries around the neck. The experiment was conducted on 33 subjects, each under totally 80 different sensor settings. The proposed approach addressed the variations of humans and devices, as well as the heterogeneous mapping between signals and SpO2 values. It identified effective device settings and characteristics of their applicable subject groups (i.e., subject inclusion-exclusion criteria). Overall, it reduced the root mean squared error (RMSE) by 16%, compared to an empirical formula and a plain SpO2 estimation model.

Laboratory Criteria for Exclusion and Readmission of Potentially Infectious Persons in Sensitive Settings in the Age of Culture-Independent Diagnostic Tests: Report of a Multidisciplinary Workgroup.

Culture-independent diagnostic tests (CIDTs) are increasingly used for clinical diagnosis of gastrointestinal diseases such as salmonellosis, Shiga toxin-producing E. coli disease, and shigellosis because of their speed, convenience, and generally high-performance characteristics. These tests are also used to screen potentially infectious asymptomatic persons during outbreak investigations in sensitive settings such as childcare, food service, and healthcare. However, only limited performance data are available for CIDTs used on specimens from asymptomatic persons. The Association of Public Health Laboratories (APHL) and Council of State and Territorial Epidemiologists (CSTE) convened a workgroup to examine the available scientific data to inform interim decision-making related to exclusion and readmission criteria for potentially infectious persons in sensitive settings, the risks and benefits of different testing strategies, and to identify knowledge gaps for further research. This is the report on the Workgroup findings.

Eligibility of emergency psychiatry patients for clinical trials studying depression.

BACKGROUND: Differences often exist between people with depression who are eligible for clinical trials and those seen in clinical practice. The impact of exclusion criteria on eligibility has been previously reported for inpatients and outpatients, but has not been assessed for emergency psychiatry patients; a group that overlaps with inpatients and outpatients but also has important distinctives. Understanding the frequencies of commonly used exclusion criteria in this population could inform interpretation of existing data (generalizability) and highlight opportunities/needs for future trials. METHODS: We reviewed 67 clinical trials studying depression using Qualitative Content Analysis to identify common and recurring exclusion criteria. We examined the frequency of these exclusion criteria among a clinical sample of emergency psychiatry patients. RESULTS: Most clinical trials had exclusions for basic research requirements, age, symptom severity, psychosis, and substance use. Applying 9 commonly used exclusion criteria to the clinical population resulted in a 3.3 % eligibility rate (95 % CI 1.2 %-7.0 %). Exclusions for psychosis (85.1 % of trials), substance use (83.6 % of trials), and suicide risk (65.7 % of trials) would likely exclude 93 % of emergency psychiatry patients. The prevalence of psychosis, substance use, and suicide risk was much higher among emergency psychiatry patients than among previously studied populations. LIMITATIONS: Some eligibility criteria could not be measured. The Qualitative Content Analysis consolidated similar exclusion criteria, losing potentially important nuances in wordings. CONCLUSIONS: Exclusion criteria commonly used in contemporary clinical trials of depression limit generalizability to emergency psychiatry patients, due in large part to exclusions for psychosis, substance use, and suicide risk.

Impaired decision-making in borderline personality disorder.

Introduction: Borderline personality disorder (BPD) is a complex mental disorder with core symptoms like interpersonal instability, emotion dysregulation, self-harm, and impulsive decision-making. Previous neuropsychological studies have found impairment in the decision-making of patients with BPD related to impulsivity. In our study, we focus on a better, more nuanced understanding of impulsive decision-making in BPD with the help of Rogers' decision-making test that simulates a gambling situation. Methods: A novelty of our study is that we excluded from further analysis non-compliant participants based on their performance. Outlier participants on the measures proportion of good choices and average of wager choice number were filtered out to represent the population that understood the basic premise of the task and showed minimal motivation to gain rewards. Thus participants often choosing the less likely color or frequently choosing the first bet amount available (to probably speed up the test) were omitted from further analysis. Another novelty is that we assessed and reported six variables that examine Deliberation Time, Quality of Decision, Risk-taking, Overall proportion bet, Delay aversion, and Risk adjustment. Forty-three women with BPD participated in the study, and 16 non-compliant were excluded. As for the healthy control group, 42 women participated in the study, and four non-compliant were excluded. Thus, we compared the data of 27 patients with BPD with 38 healthy controls. Results: Our results show that there are significant differences amongst the groups regarding the Quality of Decision Making (F (1,63) = 5.801, p = 0.019) and Risk Adjustment (F (1,63) = 6.522, p = 0.013). We also found significant interactions between group and winning probability regarding Risk Taking (F (4,252) = 4.765 p = 0.001) and Overall proportion of bets, i.e., the average proportion of bets relative to the total score of the subject (F (4,252) = 4.505, p = 0.002). Discussion: Our results show that the two groups use different decision-making strategies that can have various associations with everyday life situations.

Testing the "RCT augmentation" methodology: A trial simulation study to guide the broadening of trials eligibility criteria and inform on effectiveness.

Background: Exclusion criteria that are treatment effect modifiers (TEM) decrease RCTs results generalisability and the potentials of effectiveness estimation. In "augmented RCTs", a small proportion of otherwise-excluded patients are included to allow for effectiveness estimation. In Hodgkin Lymphoma (HL) RCTs, older age and comorbidity are common exclusion criteria, while also TEM. We simulated HL RCTs augmented with age or comorbidity, and explored in each scenario the impact of augmentation on effectiveness estimation accuracy. Methods: Simulated data with a population of HL individuals initiating drug A or B was generated. There were drug-age and drug-comorbidity interactions in the simulated data, with a greater magnitude of the former compared to the latter. Multiple augmented RCTs were simulated by randomly selecting patients with increasing proportions of older, or comorbid patients. Treatment effect size was expressed using the between-group Restricted Mean Survival Time (RMST) difference at 3 years. For each augmentation proportion, a model estimating the "real-world" treatment effect (effectiveness) was fitted and the estimation error measured (Root Mean Square Error, RMSE). Results: In simulated RCTs including none (0%), or the real-world proportion (30%) of older patients, the interquartile range of RMST difference was 0.4-0.5 years and 0.2-0.3 years, respectively, and RMSE were 0.198 years (highest possible error) and 0.056 years (lowest), respectively. Augmenting RCTs with 5% older patients decreased estimation error substantially (RMSE = 0.076 years). Augmentation with comorbid patients proved less useful for effectiveness estimation. Conclusion: In augmented RCTs aiming to inform the effectiveness of drugs, augmentation should concern in priority those exclusion criteria of suspected important TEM magnitude, so as to minimie the proportion of augmentation necessary for good effectiveness estimations.

Eligibility criteria in clinical trials in breast cancer: a cohort study.

BACKGROUND: Breast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status. METHODS: Data on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression. RESULTS: Our analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts (p > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older. CONCLUSIONS: Many recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.

A Note on Cherry-Picking in Meta-Analyses.

We study selection bias in meta-analyses by assuming the presence of researchers (meta-analysts) who intentionally or unintentionally cherry-pick a subset of studies by defining arbitrary inclusion and/or exclusion criteria that will lead to their desired results. When the number of studies is sufficiently large, we theoretically show that a meta-analysts might falsely obtain (non)significant overall treatment effects, regardless of the actual effectiveness of a treatment. We analyze all theoretical findings based on extensive simulation experiments and practical clinical examples. Numerical evaluations demonstrate that the standard method for meta-analyses has the potential to be cherry-picked.

Revisiting Exclusion of Prior Cancer in Clinical Trials of Male Breast Cancer.

Background: Eligibility criteria for cancer clinical trials present challenges to enrollment. Many trials exclude patients with a prior cancer. This common practice may be especially detrimental to trials of rare cancers, such as male breast cancer, that struggle to accrue adequate numbers of participants. Objectives: To estimate prevalence of prior cancer among men newly diagnosed with breast cancer and describe characteristics of men with prior cancer compared to those without. Methods: We identified men diagnosed with breast cancer between 2011-2015 using population-based data from National Cancer Institute's Surveillance, Epidemiology, and End Results program of cancer registries. We used sequence number and diagnosis year to identify cancers diagnosed prior to breast cancer (inclusive of prior breast, different, and unknown types of cancer). We compared sociodemographic, tumor, and treatment characteristics of men with and without prior cancer using chi-square tests. Results: Among 2317 men, nearly one quarter (24.3%) had any prior cancer, and the majority (58.7%) of these were of a different cancer type. A higher proportion of men with a prior cancer of a different type were older, had smaller (≤ 2 cm) breast tumors, were diagnosed with stage 0-1 breast cancer, and did not receive surgery compared to men without any prior cancer; there were no statistically significant differences by race and ethnicity, county median income, hormone receptor status, or surgery type. Conclusion: Given prevalence of prior cancer in this rare and understudied population of men diagnosed with breast cancer, including men with prior cancer in clinical trials may improve accrual.

Heterogeneity of BCG unresponsive bladder cancer clinical trials limits patients' access to novel therapeutics.

INTRODUCTION: Effective therapies for patients with nonmuscle invasive bladder cancer that recurs or progresses after Bacille Calmette-Guérin (BCG) are lacking. This unmet need is the focus of many drug development efforts, reflected in many completed/ongoing/planned clinical trials for patients with BCG unresponsive bladder cancer. Though BCG unresponsive criteria are well defined, enrollment criteria are variable such that, even at centers with several open trials in this space, a given patient with BCG unresponsive bladder cancer might not qualify for any. To understand the scope of this dilemma, we systematically analyzed enrollment criteria for all BCG unresponsive protocols registered on ClinicalTrials.gov to quantify heterogeneity in enrollment criteria and to determine what proportion of trials were inclusive to patients meeting U.S. Food and Drug Administration (FDA) BCG unresponsive criteria. METHODS: The ClinicalTrials.gov search tool was queried for relevant trials using the terms "bladder cancer" "nonmuscle invasive bladder cancer" and "BCG". Previously published review articles were cross-referenced to ensure that search results were comprehensive. Inclusion and exclusion criteria for the resulting 31 protocols pertaining to distinct categories such as performance status, laboratory parameters, co-morbidities, active medications, and prior therapies were recorded. Based on enrollment criteria, the trial was assessed as fully inclusive or not to patients considered to be BCG unresponsive by the 2018 FDA criteria. RESULTS: Of 31 trials, 15 (48%) had inclusion/exclusion criteria that were fully consistent with (inclusive of patients that met) the BCG unresponsive bladder cancer definition. 18 (58%) of trials excluded patients with a history of prior pelvic radiation therapy. 14 (45%) of trials excluded patients with ECOG performance status >2 (or Karnofsky Performance Status equivalent). The most common disease specific exclusion for patients with BCG unresponsive bladder cancer was a requirement for stage Tis (carcinoma in situ, CIS), which pertained to 7 (23%) of trials. CONCLUSIONS: Enrollment criteria for patients with BCG unresponsive bladder cancer are highly variable. Over half of trials evaluated do not meet stringent criteria for this disease state based upon treatment history and cancer staging requirements. For patients who desire to enroll in clinical trials, this restricts access to novel agents. For bladder cancer treating physicians and regulatory bodies, this also hinders comparisons across agents.

A review of research on eligibility criteria for clinical trials.

The purpose of this paper is to systematically sort out and analyze the cutting-edge research on the eligibility criteria of clinical trials. Eligibility criteria are important prerequisites for the success of clinical trials. It directly affects the final results of the clinical trials. Inappropriate eligibility criteria will lead to insufficient recruitment, which is an important reason for the eventual failure of many clinical trials. We have investigated the research status of eligibility criteria for clinical trials on academic platforms such as arXiv and NIH. We have classified and sorted out all the papers we found, so that readers can understand the frontier research in this field. Eligibility criteria are the most important part of a clinical trial study. The ultimate goal of research in this field is to formulate more scientific and reasonable eligibility criteria and speed up the clinical trial process. The global research on the eligibility criteria of clinical trials is mainly divided into four main aspects: natural language processing, patient pre-screening, standard evaluation, and clinical trial query. Compared with the past, people are now using new technologies to study eligibility criteria from a new perspective (big data). In the research process, complex disease concepts, how to choose a suitable dataset, how to prove the validity and scientific of the research results, are challenges faced by researchers (especially for computer-related researchers). Future research will focus on the selection and improvement of artificial intelligence algorithms related to clinical trials and related practical applications such as databases, knowledge graphs, and dictionaries.

Elevated serum transaminases in patients with acute coronary syndromes: Do we need a revision of exclusion criteria for clinical trials?

BACKGROUND: Elevations of hepatic transaminase (serum alanine transaminase [ALT] and serum aspartate aminotransferase [AST]) levels in patients with acute coronary syndrome (ACS), although transient, may result in exclusions from clinical efficacy trials due to suspected liver disease. The aim of this study was to evaluate the concentrations of serum transaminases in ACS and relate these to currently accepted AST/ALT exclusion criteria from clinical trials. METHODS: One hundred consecutive patients with ACS were prospectively examined. Blood samples for AST, ALT, total bilirubin and troponin I concentration were obtained at the time of admission and after 6, 12 and 24 hours. RESULTS: Eighty percent of patients had elevated AST, and 47% ALT; 43% of patients characterized AST concentration > 3 × upper limit of normal (ULN) in at least one measurement, while 8% of patients presented ALT concentration > 3 × ULN. AST presented higher concentrations when compared to ALT, resulting in a high De-Ritis ratio at every time point. No significant or high correlations were found between the concentrations of serum transaminases, De-Ritis ratio and troponin I. Two different cut-off values of troponin I were adopted to define the amount of infarcted myocardium that distinguished 28-31% of individuals with "large infarction". Among these patients, approximately 93% presented AST concentrations > 3 × ULN. CONCLUSIONS: Hepatic transaminases are often elevated in ACS, with the majority of patients with more extensive myocardial injury presenting high concentrations of AST. In the setting of ACS, current transaminase thresholds for liver dysfunction used in clinical trials may lead to excessive and inadequate exclusions of patients with larger infarcts from such trials.

Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria.

Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.